Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in Seveso

- A 1976 factory explosion in Seveso, Italy exposed residents to high levels of TCDD.
- The Seveso Women's Health Study follows these TCDD-exposed women over 30 years.
- We examined the relation of TCDD in 1976 and at pregnancy with pregnancy outcomes.
- TCDD levels at pregnancy were not related to adverse pregnancy outcomes.
- Initial TCDD levels were non-significantly inversely related to birthweight.

Animal evidence suggests an association between exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and adverse pregnancy outcomes. Epidemiologic studies report inconsistent results, but are limited by narrow range of exposure, small sample size, and lack of a biologic measure of highest lifetime exposure. On July 10, 1976, a chemical explosion in Seveso, Italy resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women's Health Study (SWHS), a retrospective cohort of TCDD exposure and reproductive health. Individual-level TCDD was measured in serum collected soon after the explosion. After 20 years of follow-up, we found no association between maternal TCDD in 1976 serum or estimated at pregnancy and spontaneous abortion (SAB), fetal growth, or gestational length. Here, we present an updated analysis of TCDD exposure and adverse pregnancy outcomes from a subsequent follow-up of the SWHS cohort in 2008-2009.SWHS women had 1211 post-explosion pregnancies through the 2008-2009 follow-up. We found no association between TCDD estimated at pregnancy and SAB, fetal growth, or gestational length. However, we found a non-significant inverse association between maternal 1976 serum TCDD and birthweight (adjusted β = − 22.8, 95% CI: − 80.1, 34.6). The association was stronger among first post-explosion births, but remained non-significant (adjusted β = − 47.7, 95% CI: − 107.3, 11.9). SWHS is the first study to be able to consider two potentially relevant measures of TCDD exposure: highest lifetime dose and in utero. Our results, although non-significant, suggest that highest dose may be more relevant in epidemiologic studies of TCDD and pregnancy outcomes.